1. Field of the Invention
At least one embodiment of the invention is related to a heart stimulator.
2. Description of the Related Art
Cardiac resynchronization therapy (CRT) is emerging as one of the primary treatments for patients with heart failure (HF). Numerous methods have been proposed and/or developed for optimal programming of the CRT devices, with particular focus on two timing parameters: atrio-ventricular delay (AVD), and the inter-ventricular delay (VVD).
Heart failure is a progressive disease that ultimately leads to ventricular dysfunction. Through the course of ventricular remodeling process, the ventricular geometry changes, which further causes conduction system abnormalities, for example, the inter- or intra-ventricular conduction delays. Consequently, contraction is no longer organized or synchronous between the left ventricle (LV) and right ventricle (RV), or within the LV and within RV or within the LV or within the RV or combinations thereof, leading to ventricular dyssynchrony.
The CRT is a proven technique for treating HF patients with cardiac dyssynchrony. In addition to conventional RV pacing, the LV is also paced by implanting a pacing lead through a transvenous approach via the coronary sinus (CS). By electrically stimulating the site of late ventricular activation, forcing the RV and LV to contract in a synchronized manner, the CRT can create a synchronized pumping of the ventricles, thus increasing the efficiency of ventricular contraction and improving the hemodynamics.
Nonetheless, clinical experience has shown that about one third of the CRT candidates are non-respondents, and the possible reasons may include inappropriate CS lead location, regional LV infarction, non-optimal pacing parameter settings, etc. Evidence has shown that optimizing pacing parameters, particularly the AVD and VVD, may change some CRT non-respondents to respondents. Even for the respondents, the AVD and VVD optimization may further improve the efficacy of the CRT.
The AVD optimization, which aims to maintain synchronized timing between the atria and ventricles, has been a focus of research since the early development of the dual-chamber pacemakers two decades ago. The introduction of CRT in the late 1990s has generated further interests in AVD optimization. In addition, it has brought a new challenge for VVD optimization, which aims to coordinate RV and LV contractions. Moreover, the AVD and VVD optimizations have been further complicated by other confounding factors, for example the pacing rate and the pacing mode.
Therefore a typical pacemaker is a heart stimulator that has at least one stimulation pulse generator to selectively generate stimulation pulse for delivery to at least two different chambers of a heart, said chambers include right and left atria and right and left ventricles. Said one stimulation pulse generator may be switchable in order to generate stimulation pulses for different chambers of the heart. In general, however, separate stimulation pulse generators will be provided for each heart chamber to be stimulated. The timing and triggering of stimulation pulses is typically controlled by a control unit. Time intervals to be timed by the control unit may inter alia include an atrioventricular time delay (AVD) between an atrial event and a ventricular event and/or an interventricular delay (VVD) between a right ventricular event and a left ventricular event.
State of the art pacemakers include means to optimize the atrioventricular and/or the interventricular delay based on a hemodynamic sensor information.
For AVD optimization the pacemaker provides for at least one atrial and one ventricular channel for pacing and/or sensing. For VVD optimization the pacemaker provides for pacing channels for both ventricles.
In a healthy heart, initiation of the cardiac cycle normally begins with depolarization of the sinoatrial (SA) node. This specialized structure is located in the upper portion of the right atrium wall and acts as a natural “pacemaker” of the heart. In a normal cardiac cycle and in response to the initiating SA depolarization, the right atrium contracts and forces the blood that has accumulated therein into the ventricle. The natural stimulus causing the right atrium to contract is conducted to right ventricle via the atrioventricular node (AV node) with a short, natural delay, the atrioventricular delay (AV-delay, AVD). Thus a short time after the right atrial contraction (a time sufficient to allow the bulk of the blood in the right atrium to flow through the one-way valve into the right ventricle), the right ventricle contracts, forcing the blood out of the right ventricle to the pulmonary artery. A typical time interval between depolarization of the right atrium and depolarization of the right ventricle might be 160 ms or 60 ms; a typical time interval between depolarization of the right ventricle and the next depolarization of the right atrium might be 800 ms. Thus, it is an right atrial depolarization (A), followed a relatively short time thereafter by a right ventricle depolarization (V), followed a relatively long time thereafter by the next right atrial depolarization, that produces the desired AV synchrony. Where AV synchrony exists, the heart functions very efficiently as a pump in delivering life-sustaining blood to body tissue; where AV synchrony is absent, the heart functions as an inefficient pump.
The term depolarization shall include the mechanical reaction of the tissue, the contraction, where appropriate.
Similarly, the left ventricle contracts in synchrony with right atrium and the right ventricle with a positive or negative time delay between a right ventricular contraction and a left ventricular contraction.
Also important is to address left-side AV synchrony (LA-LV).
A pacemaker generally shall induce a depolarization of a heart chamber by delivery of a stimulation pulse (pacing pulse) to said chamber when no natural (intrinsic) depolarization of said chamber occurs in due time. A depolarization of a heart chamber often is called “event”. Since a depolarization may be an intrinsic depolarization, which can be sensed by an according sensing stage of a pacemaker, such event is called a sensed event. A depolarization due to delivery of a stimulation pulse is called a paced event. A sensed event in the atrium is called As, a paced atrial event is called Ap. Similarly, a sensed event in the ventricle is called Vs and a paced ventricular event is called Vp.
To mimic the natural behavior of a heart, a dual-chamber pacemaker provides for an AV-delay timer to provide for an adequate time delay (AV-delay, AVD) between a natural (intrinsic) or a stimulated (paced) right atrial depolarization and a right ventricular depolarization. In a similar way a biventricular pacemaker provides for an adequate time delay (VV-delay, VVD) between a right ventricular depolarization and a left ventricular depolarization.
The time delay for a left ventricular (stimulated, paced) contraction may be timed from a scheduled right ventricular contraction, which has not yet occurred or from a natural (intrinsic) or a stimulated (paced) right atrial contraction. In the latter case a left ventricular stimulation pulse is scheduled by a time interval AVD+VVD, where VVD may be a positive value (RV is paced before LV), or a negative value (LV is paced before RV), or zero (RV and LV are paced simultaneously).
To deal with possibly occurring natural (intrinsic) atrial or ventricular contractions, a demand pacemaker schedules a stimulation pulse for delivery at the end of the AV-delay or the VV-delay, respectively. The delivery of said stimulation pulse is inhibited, if a natural depolarization of the heart chamber to be stimulated is sensed within the respective time delay.
Ventricular pacing in one or both ventricles is required for patients with AV-block and for CHF patients that are indicated for cardiac resynchronization therapy (CRT). For patients with intact sinus rhythm or with effective atrial pacing it is beneficial to stimulate the ventricle(s) synchronous with the atrial activation, i.e., with a certain delay period after the atrial event. Standard AV-synchronous dual- or three-chamber implantable devices have a programmable AVD that can be adjusted by the physician. Several studies have shown the importance of individual AVD optimization to improve the cardiac output. Especially for CHF patients an optimization of the AVD is essential. As the pumping efficacy is impaired, the optimal timing of the ventricular stimulus in relation to the atrial event contributes significantly to the cardiac performance. If the AVD is too short, the ventricle contracts before it is completely filled by the atrial blood inflow. The active filling time is reduced. Hence the stroke volume and the cardiac output are reduced. If the AVD is too long, the ventricle contracts a while after the closure of the atrioventricular valve. Hence the passive filling time of the ventricle, i.e., the diastolic filling period during the myocardial relaxation before the atrial kick, is decreased. Also backflow of blood from the ventricle into the atrium, e.g., mitral regurgitation, is likely. Thus also in this case cardiac output (CO) is reduced. Similar to the heart rate, the optimal AVD also depends on the autonomic tone. If the sympathetic tone is high, e.g., during exercise, the optimal AVD is shortened compared to the resting value.
Patients with CHF and Left Bundle-Branch Block (LBBB), i.e., with intra- or inter-ventricular dyssynchrony expressed by a widened QRS complex in the electrogram may benefit from biventricular pacing. Pacing both ventricles simultaneously or with a certain VVD restores the synchrony of the ventricles and thus improves the hemodynamic performance. Also mitral regurgitation is reduced by biventricular pacing. Recent CRT pacing devices, implantable pulse generators (IPGs) or ICDs, offer a programmable VVD parameter. The delay time between the right ventricular (RV) and left ventricular (LV) stimulation can be programmed, usually approx. in the range −100 ms . . . +100 ms. The sign determines whether the RV or the LV is paced first. Zero ms, or 0 ms means simultaneous pacing of both ventricles. Also RV or LV-only pacing can be programmed. It has been found that the setting that results in optimal hemodynamics varies from patient to patient. The optimal value also depends on the individual position of the left ventricular pacing lead.
Some prior art pacemaker includes at least one impedance measuring stage being connected to electrodes or a connector for such electrodes to measure an intracardiac or intrathoracic impedance when in use.
For CRT optimization presently the following techniques are applied:
Conventionally, the AVD optimization in clinical practice has been achieved using echocardiographic techniques, particularly by measuring the pulse-wave Doppler signals of the mitral inflow. The most representative technique is the Ritter method, which estimates the optimal AVD based on the measured interval from the QRS onset to the end of A wave (active filling). Some variants of the Ritter method have also been proposed. Alternatively, the optimal AVD can be estimated, by maximizing the velocity time integral (VTI) of the aortic outflow or the mitral inflow. In addition, other Doppler-based methods for AVD optimization have also been explored, based on estimation of the cardiac output, the LV pressure derivative dP/dt, and the derived myocardial performance index (MPI), which is defined as the ratio of isovolumic contraction time plus the isovolumic relaxation time to the ejection time. Another non-invasive method for assessment of cardiac output is the thoracic impedance cardiography, which has been used for optimizing the AVD, and was found to give similar results as echocardiography. Recently, finger photoplethysmography as a simple method for non-invasive blood pressure monitoring, has been shown to be another attractive tool for optimizing AVD in CRT devices.
Alternatively, the AVD can be optimized based on hemodynamic indexes that are assumed to correlate to the stroke volume or cardiac output, such as the blood pressure or its temporal derivative, the ventricular volume (e.g., through chamber impedance measurement), the blood oxygen saturation, blood pH, blood temperature, etc.
The AVD and VVD can also be optimized based on some metrics derived from the surface ECG or intracardiac electrogram (IEGM) signal. For example, St. Jude Medical has developed the QuickOpt algorithm, which calculates the optimal AVD based on the measurement of P wave duration (PWD) from the surface ECG. An empirical formula was developed to calculate the optimal VVD based on the difference between left- and right-side AV conduction times and the inter-ventricular conduction times. In another example, Boston Scientific's EEHF+ algorithm calculates the optimal AVD based on patient's QRS width, the intrinsic AV interval, and the LV lead location and the pacing chamber. The optimal VVD is also empirically determined based on the difference between left- and right-side AV conduction times.
The importance of inter-atrial conduction time (IACT) on AVD optimization has long been recognized. The IACT is a critical interval in the interaction between left atrium (LA) emptying and LV filling. Programming AVD that is excessively longer than IACT will frequently cause diastolic mitral regurgitation, whereas programming AVD that is shorter than IACT will frequently cause P wave reversal or increased venous and pulmonary pressure because of atrial contraction against a closed mitral valve. The IACT can be approximate by the PWD, which could be measured on surface ECG or IEGM recorded from far-field sensing vectors. Studies have suggested that there may be a linear relationship between IACT and optimal AVD.
Studies have shown that the efficacy of CRT is related the site of LV pacing. While the selection of optimal LV pacing site is limited by the coronary venous anatomy, the introduction of multi-polar LV leads may offer more options to choose different LV pacing vectors that could potentially improve the cardiac hemodynamics.
Most non-invasive methods described above share two common disadvantages. First, AVD optimization can only be performed after initial implantation or during device follow-up, when specially trained technicians are present to operate the external devices for the measurement. Second, patients are required to remain sedated or in stable supine position during the entire optimization procedure, which is time-consuming. Therefore, on one hand, it adds to the already high cost of the CRT. On the other hand, the AVD optimized in such well-controlled environment is unlikely to be optimal in the ambulatory conditions.
The AVD optimization methods based on measurement of hemodynamic parameters usually require special sensors, and their technically reliability has not been proven.
The QuickOpt algorithm assumes there is a linear relationship between optimal AVD and the PWD. The EEHF+ algorithm assumes the optimal AVD is linearly related to QRS width and intrinsic AV interval. These assumptions do not consider the electrical-mechanical coupling of the myocardium, thus the AVD determined based on the timing of electrical events may not correspond to the optimal AV timing for the mechanical events of the heart. In fact, the recent Trials showed that the optimal AVD determined using these methods was not superior to empirically programmed AVD.
Typically, the IACT measurement requires special sensors or echo equipment. Moreover, previous studies failed to demonstrate sufficiently high correlation coefficient of the linear regression model between IACT and the optimal AVD. Therefore, significant deviance may exist between the model predicted optimal AVD and the truly optimal AVD. Similarly, this approach failed to consider the timing of mechanical events of the heart.
How to determine the optimal LV pacing site remains unclear. Although the general principle is to pace in the region with the most delayed activation and to avoid pacing in the infarct area, there is no proven guidance on how to achieve this.